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Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy

A common complication of both type I and type II diabetes is nephropathy, characterized by accumulation of extracellular matrix in the glomerular mesangium. This indicates a central role of mesangial cells in the pathophysiology of diabetic nephropathy. Using the proteomic approach, it was earlier e...

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Autores principales: Feng, Ying, Ming-yue, Jin, Dong-wei, Liu, Wei, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209586/
https://www.ncbi.nlm.nih.gov/pubmed/30287505
http://dx.doi.org/10.1042/BSR20180815
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author Feng, Ying
Ming-yue, Jin
Dong-wei, Liu
Wei, Li
author_facet Feng, Ying
Ming-yue, Jin
Dong-wei, Liu
Wei, Li
author_sort Feng, Ying
collection PubMed
description A common complication of both type I and type II diabetes is nephropathy, characterized by accumulation of extracellular matrix in the glomerular mesangium. This indicates a central role of mesangial cells in the pathophysiology of diabetic nephropathy. Using the proteomic approach, it was earlier elucidated in a rat model that the proteasome subunit-α type-6 protein (PSMA6) is suppressed in the renal cortex in nephropathic kidney. However, the underlying mechanism effecting suppression of PSMA6 protein in the renal cortex is not yet known. Twenty diabetic patients were enrolled and the expression level of PSMA6 in them was detected by immunohistochemistry. The protein and mRNA expression levels of PSMA6 in NRK-52E cells under high glucose condition were determined by Western blot and quantitative real-time PCR, respectively. Dual luciferase assay was used to detect the relationship of PSMA6 and miR-4490. Our results show that PSMA6 protein is down-regulated in patients with diabetic nephropathy compared with healthy control. Using the NRK-52E cell line cultured under high glucose condition as an in vitro model of diabetic nephropathy, we show that loss of PSMA6 protein expression occured independent of changes the in PSMA6 mRNA expression. We next elucidate that PSMA6 mRNA is post-transcriptionally regulated by the microRNA (miRNA)-4490, whose expression is inversely correlated to PSMA6 protein expression. Using reporter assays we show that PSMA6 is a direct target of the miR-4490. Exogenous manipulation of miR-4490 levels modulated expression of PSMA6, indicating that miR-4490 can be tested as a biomarker for nephropathy in diabetic patients.
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spelling pubmed-62095862018-11-14 Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy Feng, Ying Ming-yue, Jin Dong-wei, Liu Wei, Li Biosci Rep Research Articles A common complication of both type I and type II diabetes is nephropathy, characterized by accumulation of extracellular matrix in the glomerular mesangium. This indicates a central role of mesangial cells in the pathophysiology of diabetic nephropathy. Using the proteomic approach, it was earlier elucidated in a rat model that the proteasome subunit-α type-6 protein (PSMA6) is suppressed in the renal cortex in nephropathic kidney. However, the underlying mechanism effecting suppression of PSMA6 protein in the renal cortex is not yet known. Twenty diabetic patients were enrolled and the expression level of PSMA6 in them was detected by immunohistochemistry. The protein and mRNA expression levels of PSMA6 in NRK-52E cells under high glucose condition were determined by Western blot and quantitative real-time PCR, respectively. Dual luciferase assay was used to detect the relationship of PSMA6 and miR-4490. Our results show that PSMA6 protein is down-regulated in patients with diabetic nephropathy compared with healthy control. Using the NRK-52E cell line cultured under high glucose condition as an in vitro model of diabetic nephropathy, we show that loss of PSMA6 protein expression occured independent of changes the in PSMA6 mRNA expression. We next elucidate that PSMA6 mRNA is post-transcriptionally regulated by the microRNA (miRNA)-4490, whose expression is inversely correlated to PSMA6 protein expression. Using reporter assays we show that PSMA6 is a direct target of the miR-4490. Exogenous manipulation of miR-4490 levels modulated expression of PSMA6, indicating that miR-4490 can be tested as a biomarker for nephropathy in diabetic patients. Portland Press Ltd. 2018-10-31 /pmc/articles/PMC6209586/ /pubmed/30287505 http://dx.doi.org/10.1042/BSR20180815 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Feng, Ying
Ming-yue, Jin
Dong-wei, Liu
Wei, Li
Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title_full Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title_fullStr Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title_full_unstemmed Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title_short Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy
title_sort proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microrna-4490 in diabetic nephropathy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209586/
https://www.ncbi.nlm.nih.gov/pubmed/30287505
http://dx.doi.org/10.1042/BSR20180815
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